OMIA 001683-9615 : Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611927 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific name: Dry eye curly coat syndrome

Species-specific symbol: CKCSID

Mapping: By conducting a GWAS on 23 affected and 38 control Cavalier King Charles Spaniels, each genotyped with the Illumina Canine HD SNP chip (yielding 91,427 SNPs for analysis), Forman et al. (2012) highlighted a region on chromosome CFA13.

Molecular basis: By sequencing their candidate region (see Mapping section) in affected and normal dogs, Forman et al. (2012) eventually revealed the causative mutation as a "single base deletion in exon 5" in a gene with the somewhat unusual name of Family with sequence similarity 83, member H (FAM83H). Using the genetic variant nomenclature as of 2015, the cuastaive variant can be descripted as c.977delC or p.Pro326Hisfs*258.

Clinical features: CKCSID presents as a combination of two primary disease processes:

Keratoconjunctivitis sicca: Decreased tear production leads to drying of the surface of the eye. Common signs include redness in one or both eyes, with a thick mucoid discharge. Chronic dry eyeball surfaces often predisposes to corneal ulceration and further painful secondary bacterial conjunctivitis (Barnett, 2006).

Ichythyosiform dermatosis: Typically presents as a rough and curly coat with possible multifocal alopecia. The epidermis is generally dry, scale-like, and flakes off, particularly around the dorsal spine and lateral flankregion. The abdominal venter may be hyperpigmented, whilst the footpads typically show signs of hyperkeratinization. The nails may present with marked growth abnormalities (Hartley et al., 2012).

[IT thanks DVM student Tom Spunar, who provided the basis of this contribution in April 2022]

Pathology: Keratoconjunctivitis sicca develops as a result of decreased aqueous tear production and mucin secretion, leading to progressive loss of the precorneal tear film (PTF) This predisposes it to damage and infection. The exact pathway is poorly understood, but is thought to be due to a neurofunctional abnormality in the lacrimal glands of affected dogs. Dryness and the loss of the tear film leads to profound irritation, diffuse hyperaemia and predisposes secondary conjunctivitis (Hartley et al., 2012).

Ichythyosiform dermatosis is characterized as a cutaneous scaling and hyperkeratinization disorder. It develops due to an abnormal rate of cell turnover in outer layer of epidermis, the stratum corneum. Hyperplastic dysregulation of these cells culminates in a loss of the epithelial ‘brick and mortar’ structure. This increased cellular turnover leads to progressive drying and flaking of exterior layers which is exacerbated by increased lipid deposition and further inflammatory mediators (Mauldin, 2013).

[IT thanks DVM student Tom Spunar, who provided the basis of this contribution in April 2022]

Breed: Cavalier King Charles Spaniel.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FAM83H family with sequence similarity 83, member H Canis lupus familiaris 13 NC_051817.1 (37804968..37796064) FAM83H Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
460 Cavalier King Charles Spaniel Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis FAM83H deletion, small (<=20) Naturally occurring variant CanFam3.1 13 g.37328057del c.977del p.(P326Hfs*258) NM_001289427.1; NP_001276356.1; genomic position in accordance with HGVS 3'-rule 2012 22253609 Genomic coordinates in CanFam3.1 provided by Zoe Shmidt and Robert Kuhn.

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Nimmo, J.S., McMillan, E., Sofronidis, G. :
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in a Cavalier King Charles spaniel with a single defective copy of the FAM83H gene. Aust Vet Pract 50:41-46, 2020.
2019 Lewis, T.W., Mellersh, C.S. :
Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.
2017 Guandalini, A., Di Girolamo, N., Corvi, R., Santillo, D., Andreani, V., Pinzo, B. :
Epidemiology of ocular disorders presumed to be inherited in three small Italian dog breeds in Italy. Vet Ophthalmol 21:524-529, 2017. Pubmed reference: 29284193. DOI: 10.1111/vop.12542.
2012 Forman, O.P., Penderis, J., Hartley, C., Hayward, L.J., Ricketts, S.L., Mellersh, C.S. :
Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed. PLoS Genet 8:e1002462, 2012. Pubmed reference: 22253609. DOI: 10.1371/journal.pgen.1002462.
Hartley, C., Barnett, K.C., Pettitt, L., Forman, O.P., Blott, S., Mellersh, C.S. :
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Cavalier King Charles spaniel dogs. Part II: candidate gene study. Vet Ophthalmol 15:327-32, 2012. Pubmed reference: 22339941. DOI: 10.1111/j.1463-5224.2012.00987.x.
Hartley, C., Donaldson, D., Smith, K.C., Henley, W., Lewis, T.W., Blott, S., Mellersh, C., Barnett, K.C. :
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs. Part I: clinical signs, histopathology, and inheritance. Vet Ophthalmol 15:315-26, 2012. Pubmed reference: 22212237. DOI: 10.1111/j.1463-5224.2011.00986.x.
2006 Barnett, K.C. :
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel. J Small Anim Pract 47:524-8, 2006. Pubmed reference: 16961470. DOI: 10.1111/j.1748-5827.2006.00107.x.

Edit History


  • Created by Frank Nicholas on 16 Jan 2012
  • Changed by Frank Nicholas on 26 Jan 2012
  • Changed by Frank Nicholas on 26 Jan 2013
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Tosso Leeb on 24 Dec 2015
  • Changed by Imke Tammen2 on 22 Aug 2021
  • Changed by Imke Tammen2 on 22 May 2022